Alpha-crystallin B chain is a protein that in humans is encoded by the CRYABgene.[5] It is part of the small heat shock protein family and functions as molecular chaperone that primarily binds misfolded proteins to prevent protein aggregation, as well as inhibit apoptosis and contribute to intracellular architecture.[6][7][8] Post-translational modifications decrease the ability to chaperone.[6][8] Mutations in CRYAB cause different cardiomyopathies,[9] skeletal myopathies[10] mainly myofibrillar myopathy,[11] and also cataracts.[12] In addition, defects in this gene/protein have been associated with cancer and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.[6][7][8]
Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups.
Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Alpha crystallins are composed of two gene products: alpha-A and alpha-B, for acidic and basic, respectively. These heterogeneous aggregates consist of 30–40 subunits; the alpha-A and alpha-B subunits have a 3:1 ratio, respectively.[6]
Functionedit
Alpha B chain crystallins (αBC) can be induced by heat shock, ischemia, and oxidation, and are members of the small heat shock protein (sHSP also known as the HSP20) family.[6][13] They act as molecular chaperones although they do not renature proteins and release them in the fashion of a true chaperone; instead, they bind improperly folded proteins to prevent protein aggregation.[6][7][8]
Furthermore, αBC may confer stress resistance to cells by inhibiting the processing of the pro-apoptotic protein caspase-3.[8] Two additional functions of alpha crystallins are an autokinase activity and participation in the intracellular architecture. Alpha-A and alpha-B gene products are differentially expressed; alpha-A is preferentially restricted to the lens and alpha-B is expressed widely in many tissues and organs. Elevated expression of alpha-B crystallin occurs in many neurological diseases; a missense mutation cosegregated in a family with a desmin-related myopathy.[6]
Clinical significanceedit
Although not yet clearly understood, defective chaperone activity is expected to trigger the accumulation of protein aggregates and underlie the development of α-crystallinopathy, or the failure of protein quality control, resulting in protein deposition diseases such as Alzheimer’s disease and Parkinson’s disease. Mutations in CRYAB could also cause restrictive cardiomyopathy.[14] ER-anchored αBC can suppress aggregate formation mediated by the disease mutant. Thus, modulation of the micromilieu surrounding the ER membrane can serve as a potential target in developing pharmacological interventions for protein deposition disease.[7]
Though expressed highly in eye lens and muscle tissues, αBC can also be found in several types of cancer, among which head and neck squamous cell carcinoma (HNSCC) and breast carcinomas, as well as in patients with tuberous sclerosis.[15] αBC expression is associated with metastasis formation in HNSCC and in breast carcinomas and in other types of cancer, expression is often correlated with poor prognosis as well.[16] The expression of αBC can be increased during various stresses, like heat shock, osmotic stress or exposure to heavy metals, which then may lead to prolonged survival of cells under these conditions.[8]
^ abcGRCh38: Ensembl release 89: ENSG00000109846 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000032060 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Jeanpierre C, Austruy E, Delattre O, Jones C, Junien C (March 1993). "Subregional physical mapping of an alpha B-crystallin sequence and of a new expressed sequence D11S877E to human 11q". Mammalian Genome. 4 (2): 104–8. doi:10.1007/BF00290434. PMID 8431633. S2CID 9038111.
^ abcdYamamoto S, Yamashita A, Arakaki N, Nemoto H, Yamazaki T (December 2014). "Prevention of aberrant protein aggregation by anchoring the molecular chaperone αB-crystallin to the endoplasmic reticulum". Biochemical and Biophysical Research Communications. 455 (3–4): 241–5. doi:10.1016/j.bbrc.2014.10.151. PMID 25449278.
^ abcdefvan de Schootbrugge C, Schults EM, Bussink J, Span PN, Grénman R, Pruijn GJ, Kaanders JH, Boelens WC (April 2014). "Effect of hypoxia on the expression of αB-crystallin in head and neck squamous cell carcinoma". BMC Cancer. 14: 252. doi:10.1186/1471-2407-14-252. PMC3990244. PMID 24725344.
^Vicart, P.; Caron, A.; Guicheney, P.; Li, Z.; Prévost, M. C.; Faure, A.; Chateau, D.; Chapon, F.; Tomé, F. (September 1998). "A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy". Nature Genetics. 20 (1): 92–95. doi:10.1038/1765. ISSN 1061-4036. PMID 9731540. S2CID 24517435.
^Fichna JP, Maruszak A, Żekanowski C (November 2018). "Myofibrillar myopathy in the genomic context". Journal of Applied Genetics. 59 (4): 431–439. doi:10.1007/s13353-018-0463-4. PMID 30203143.
^Fichna JP, Potulska-Chromik A, Miszta P, Redowicz MJ, Kaminska AM, Zekanowski C, Filipek S (November 2016). "A novel dominant D109A CRYAB mutation in a family with myofibrillar myopathy affects αB-crystallin structure". BBA Clinical. 7: 1–7. doi:10.1016/j.bbacli.2016.11.004. PMC5124346. PMID 27904835.
^Easterbrook M, Trope G (1989). "Value of Humphrey perimetry in the detection of early chloroquine retinopathy". Lens and Eye Toxicity Research. 6 (1–2): 255–68. PMID 2488020.
^Brodehl A, Gaertner-Rommel A, Klauke B, Grewe SA, Schirmer I, Peterschröder A, Faber L, Vorgerd M, Gummert J, Anselmetti D, Schulz U, Paluszkiewicz L, Milting H (August 2017). "The novel αB-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy". Human Mutation. 38 (8): 947–952. doi:10.1002/humu.23248. PMID 28493373. S2CID 13942559.
^Wang F, Chen X, Li C, Sun Q, Chen Y, Wang Y, Peng H, Liu Z, Chen R, Liu K, Yan H, Ye BH, Kwiatkowski DJ, Zhang H (August 2014). "Pivotal role of augmented αB-crystallin in tumor development induced by deficient TSC1/2 complex". Oncogene. 33 (34): 4352–8. doi:10.1038/onc.2013.401. PMID 24077282.
^Moyano JV, Evans JR, Chen F, Lu M, Werner ME, Yehiely F, Diaz LK, Turbin D, Karaca G, Wiley E, Nielsen TO, Perou CM, Cryns VL (January 2006). "AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer". The Journal of Clinical Investigation. 116 (1): 261–70. doi:10.1172/JCI25888. PMC1323258. PMID 16395408.
^ abcdFu L, Liang JJ (February 2002). "Detection of protein-protein interactions among lens crystallins in a mammalian two-hybrid system assay". The Journal of Biological Chemistry. 277 (6): 4255–60. doi:10.1074/jbc.M110027200. PMID 11700327.
^Sugiyama Y, Suzuki A, Kishikawa M, Akutsu R, Hirose T, Waye MM, Tsui SK, Yoshida S, Ohno S (January 2000). "Muscle develops a specific form of small heat shock protein complex composed of MKBP/HSPB2 and HSPB3 during myogenic differentiation". The Journal of Biological Chemistry. 275 (2): 1095–104. doi:10.1074/jbc.275.2.1095. PMID 10625651.
^Kato K, Shinohara H, Goto S, Inaguma Y, Morishita R, Asano T (April 1992). "Copurification of small heat shock protein with alpha B crystallin from human skeletal muscle". The Journal of Biological Chemistry. 267 (11): 7718–25. doi:10.1016/S0021-9258(18)42574-4. PMID 1560006.
^Boelens WC, Croes Y, de Jong WW (January 2001). "Interaction between αB-crystallin and the human 20S proteasomal subunit C8/α7". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1544 (1–2): 311–9. doi:10.1016/S0167-4838(00)00243-0. PMID 11341940.
Further readingedit
Derham BK, Harding JJ (July 1999). "Alpha-crystallin as a molecular chaperone". Progress in Retinal and Eye Research. 18 (4): 463–509. doi:10.1016/S1350-9462(98)00030-5. PMID 10217480. S2CID 25124893.
Calinisan V, Gravem D, Chen RP, Brittin S, Mohandas N, Lecomte MC, Gascard P (May 2006). "New insights into potential functions for the protein 4.1 superfamily of proteins in kidney epithelium". Frontiers in Bioscience. 11: 1646–66. doi:10.2741/1911. PMID 16368544. S2CID 26325962.
External linksedit
GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy
April 15, 2024
cryab, alpha, crystallin, chain, protein, that, humans, encoded, gene, part, small, heat, shock, protein, family, functions, molecular, chaperone, that, primarily, binds, misfolded, proteins, prevent, protein, aggregation, well, inhibit, apoptosis, contribute,. Alpha crystallin B chain is a protein that in humans is encoded by the CRYAB gene 5 It is part of the small heat shock protein family and functions as molecular chaperone that primarily binds misfolded proteins to prevent protein aggregation as well as inhibit apoptosis and contribute to intracellular architecture 6 7 8 Post translational modifications decrease the ability to chaperone 6 8 Mutations in CRYAB cause different cardiomyopathies 9 skeletal myopathies 10 mainly myofibrillar myopathy 11 and also cataracts 12 In addition defects in this gene protein have been associated with cancer and neurodegenerative diseases such as Alzheimer s disease and Parkinson s disease 6 7 8 CRYABAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes2KLR 2N0K 2WJ7 2Y1Y 2Y1Z 2Y22 2YGD 3L1G 3SGM 3SGN 3SGO 3SGP 3SGR 3SGS 4M5S 4M5T 3J07IdentifiersAliasesCRYAB CMD1II CRYA2 CTPP2 CTRCT16 HEL S 101 HSPB5 MFM2 crystallin alpha BExternal IDsOMIM 123590 MGI 88516 HomoloGene 68209 GeneCards CRYABGene location Human Chr Chromosome 11 human 1 Band11q23 1Start111 908 564 bp 1 End111 923 722 bp 1 Gene location Mouse Chr Chromosome 9 mouse 2 Band9 A5 3 9 27 75 cMStart50 662 625 bp 2 End50 667 936 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inmiddle frontal gyrusolfactory bulboptic nerveinferior ganglion of vagus nerveright ventriclegastrocnemius muscletibialis anterior muscleinternal globus pallidusbody of tonguetibial nerveTop expressed inciliary bodyirismyocardium of ventriclesoleus musclesciatic nerveintercostal muscleretinal pigment epitheliummasseter muscleextraocular muscleright ventricleMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein homodimerization activity microtubule binding unfolded protein binding metal ion binding cytoskeletal protein binding protein binding structural constituent of eye lens identical protein binding amyloid beta binding protein containing complex bindingCellular componentcytoplasm Golgi apparatus I band microtubule cytoskeleton nucleoplasm cell surface actin filament bundle extracellular exosome nucleus cardiac myofibril perikaryon dendritic spine synaptic membrane synapse M band postsynaptic density axon mitochondrion cytosol plasma membrane Z disc contractile fiber protein containing complexBiological processnegative regulation of intracellular transport response to estradiol muscle contraction regulation of cell death human ageing negative regulation of apoptotic process microtubule polymerization or depolymerization protein folding stress activated MAPK cascade negative regulation of cell growth cellular response to gamma radiation regulation of cellular response to heat negative regulation of reactive oxygen species metabolic process protein homooligomerization response to hydrogen peroxide response to hypoxia lens development in camera type eye tubulin complex assembly muscle organ development multicellular organism aging negative regulation of gene expression negative regulation of protein homooligomerization camera type eye development negative regulation of cysteine type endopeptidase activity involved in apoptotic process protein stabilization apoptotic process involved in morphogenesis negative regulation of amyloid fibril formation negative regulation of transcription DNA templatedSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez141012955EnsemblENSG00000109846ENSMUSG00000032060UniProtP02511P23927RefSeq mRNA NM 001289807NM 001289808NM 001885NM 001330379NM 001368245NM 001368246NM 001289782NM 001289784NM 001289785NM 009964RefSeq protein NP 001276736NP 001276737NP 001317308NP 001876NP 001355174NP 001355175NP 001276711NP 001276713NP 001276714NP 034094Location UCSC Chr 11 111 91 111 92 MbChr 9 50 66 50 67 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Structure 2 Function 3 Clinical significance 4 Interactions 5 References 6 Further reading 7 External linksStructure editCrystallins are separated into two classes taxon specific or enzyme and ubiquitous The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens Since lens central fiber cells lose their nuclei during development these crystallins are made and then retained throughout life making them extremely stable proteins Mammalian lens crystallins are divided into alpha beta and gamma families beta and gamma crystallins are also considered as a superfamily Alpha and beta families are further divided into acidic and basic groups Seven protein regions exist in crystallins four homologous motifs a connecting peptide and N and C terminal extensions Alpha crystallins are composed of two gene products alpha A and alpha B for acidic and basic respectively These heterogeneous aggregates consist of 30 40 subunits the alpha A and alpha B subunits have a 3 1 ratio respectively 6 Function editAlpha B chain crystallins aBC can be induced by heat shock ischemia and oxidation and are members of the small heat shock protein sHSP also known as the HSP20 family 6 13 They act as molecular chaperones although they do not renature proteins and release them in the fashion of a true chaperone instead they bind improperly folded proteins to prevent protein aggregation 6 7 8 Furthermore aBC may confer stress resistance to cells by inhibiting the processing of the pro apoptotic protein caspase 3 8 Two additional functions of alpha crystallins are an autokinase activity and participation in the intracellular architecture Alpha A and alpha B gene products are differentially expressed alpha A is preferentially restricted to the lens and alpha B is expressed widely in many tissues and organs Elevated expression of alpha B crystallin occurs in many neurological diseases a missense mutation cosegregated in a family with a desmin related myopathy 6 Clinical significance editAlthough not yet clearly understood defective chaperone activity is expected to trigger the accumulation of protein aggregates and underlie the development of a crystallinopathy or the failure of protein quality control resulting in protein deposition diseases such as Alzheimer s disease and Parkinson s disease Mutations in CRYAB could also cause restrictive cardiomyopathy 14 ER anchored aBC can suppress aggregate formation mediated by the disease mutant Thus modulation of the micromilieu surrounding the ER membrane can serve as a potential target in developing pharmacological interventions for protein deposition disease 7 Though expressed highly in eye lens and muscle tissues aBC can also be found in several types of cancer among which head and neck squamous cell carcinoma HNSCC and breast carcinomas as well as in patients with tuberous sclerosis 15 aBC expression is associated with metastasis formation in HNSCC and in breast carcinomas and in other types of cancer expression is often correlated with poor prognosis as well 16 The expression of aBC can be increased during various stresses like heat shock osmotic stress or exposure to heavy metals which then may lead to prolonged survival of cells under these conditions 8 Interactions editCRYAB has been shown to interact with CRYAA 17 CRYBB2 17 CRYGC 17 HSPB2 18 Hsp27 17 19 and PSMA3 20 References edit a b c GRCh38 Ensembl release 89 ENSG00000109846 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000032060 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Jeanpierre C Austruy E Delattre O Jones C Junien C March 1993 Subregional physical mapping of an alpha B crystallin sequence and of a new expressed sequence D11S877E to human 11q Mammalian Genome 4 2 104 8 doi 10 1007 BF00290434 PMID 8431633 S2CID 9038111 a b c d e f g Entrez Gene CRYAB crystallin alpha B a b c d Yamamoto S Yamashita A Arakaki N Nemoto H Yamazaki T December 2014 Prevention of aberrant protein aggregation by anchoring the molecular chaperone aB crystallin to the endoplasmic reticulum Biochemical and Biophysical Research Communications 455 3 4 241 5 doi 10 1016 j bbrc 2014 10 151 PMID 25449278 a b c d e f van de Schootbrugge C Schults EM Bussink J Span PN Grenman R Pruijn GJ Kaanders JH Boelens WC April 2014 Effect of hypoxia on the expression of aB crystallin in head and neck squamous cell carcinoma BMC Cancer 14 252 doi 10 1186 1471 2407 14 252 PMC 3990244 PMID 24725344 Brodehl Andreas Gaertner Rommel Anna Klauke Barbel Grewe Simon Andre Schirmer Ilona Peterschroder Andreas Faber Lothar Vorgerd Matthias Gummert Jan August 2017 The novel aB crystallin CRYAB mutation p D109G causes restrictive cardiomyopathy Human Mutation 38 8 947 952 doi 10 1002 humu 23248 ISSN 1098 1004 PMID 28493373 S2CID 13942559 Vicart P Caron A Guicheney P Li Z Prevost M C Faure A Chateau D Chapon F Tome F September 1998 A missense mutation in the alphaB crystallin chaperone gene causes a desmin related myopathy Nature Genetics 20 1 92 95 doi 10 1038 1765 ISSN 1061 4036 PMID 9731540 S2CID 24517435 Fichna JP Maruszak A Zekanowski C November 2018 Myofibrillar myopathy in the genomic context Journal of Applied Genetics 59 4 431 439 doi 10 1007 s13353 018 0463 4 PMID 30203143 Fichna JP Potulska Chromik A Miszta P Redowicz MJ Kaminska AM Zekanowski C Filipek S November 2016 A novel dominant D109A CRYAB mutation in a family with myofibrillar myopathy affects aB crystallin structure BBA Clinical 7 1 7 doi 10 1016 j bbacli 2016 11 004 PMC 5124346 PMID 27904835 Easterbrook M Trope G 1989 Value of Humphrey perimetry in the detection of early chloroquine retinopathy Lens and Eye Toxicity Research 6 1 2 255 68 PMID 2488020 Brodehl A Gaertner Rommel A Klauke B Grewe SA Schirmer I Peterschroder A Faber L Vorgerd M Gummert J Anselmetti D Schulz U Paluszkiewicz L Milting H August 2017 The novel aB crystallin CRYAB mutation p D109G causes restrictive cardiomyopathy Human Mutation 38 8 947 952 doi 10 1002 humu 23248 PMID 28493373 S2CID 13942559 Wang F Chen X Li C Sun Q Chen Y Wang Y Peng H Liu Z Chen R Liu K Yan H Ye BH Kwiatkowski DJ Zhang H August 2014 Pivotal role of augmented aB crystallin in tumor development induced by deficient TSC1 2 complex Oncogene 33 34 4352 8 doi 10 1038 onc 2013 401 PMID 24077282 Moyano JV Evans JR Chen F Lu M Werner ME Yehiely F Diaz LK Turbin D Karaca G Wiley E Nielsen TO Perou CM Cryns VL January 2006 AlphaB crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer The Journal of Clinical Investigation 116 1 261 70 doi 10 1172 JCI25888 PMC 1323258 PMID 16395408 a b c d Fu L Liang JJ February 2002 Detection of protein protein interactions among lens crystallins in a mammalian two hybrid system assay The Journal of Biological Chemistry 277 6 4255 60 doi 10 1074 jbc M110027200 PMID 11700327 Sugiyama Y Suzuki A Kishikawa M Akutsu R Hirose T Waye MM Tsui SK Yoshida S Ohno S January 2000 Muscle develops a specific form of small heat shock protein complex composed of MKBP HSPB2 and HSPB3 during myogenic differentiation The Journal of Biological Chemistry 275 2 1095 104 doi 10 1074 jbc 275 2 1095 PMID 10625651 Kato K Shinohara H Goto S Inaguma Y Morishita R Asano T April 1992 Copurification of small heat shock protein with alpha B crystallin from human skeletal muscle The Journal of Biological Chemistry 267 11 7718 25 doi 10 1016 S0021 9258 18 42574 4 PMID 1560006 Boelens WC Croes Y de Jong WW January 2001 Interaction between aB crystallin and the human 20S proteasomal subunit C8 a7 Biochimica et Biophysica Acta BBA Protein Structure and Molecular Enzymology 1544 1 2 311 9 doi 10 1016 S0167 4838 00 00243 0 PMID 11341940 Further reading editDerham BK Harding JJ July 1999 Alpha crystallin as a molecular chaperone Progress in Retinal and Eye Research 18 4 463 509 doi 10 1016 S1350 9462 98 00030 5 PMID 10217480 S2CID 25124893 Calinisan V Gravem D Chen RP Brittin S Mohandas N Lecomte MC Gascard P May 2006 New insights into potential functions for the protein 4 1 superfamily of proteins in kidney epithelium Frontiers in Bioscience 11 1646 66 doi 10 2741 1911 PMID 16368544 S2CID 26325962 External links editGeneReviews NIH NCBI UW entry on Myofibrillar Myopathy Retrieved from https en wikipedia org w index php title CRYAB amp oldid 1188063219, wikipedia, wiki, book, books, library,
